Set in the Republic of Greater East Asia, an alternate-history totalitarian state resembling fascist Japan, the novel depicts a country governed by authoritarian control and quasi-seclusion. Each year, the government selects fifty ninth-grade classes to participate in the Program, a government-mandated killing game in which students must fight until only one survives. A government memo preceding the story reveals that an unauthorized intrusion into the Program's computer systems was detected months earlier, but officials decide to proceed with the upcoming trial regardless.
Shuya Nanahara, a fifteen-year-old orphan and aspiring rock musician, rides a bus with his 41 classmates from Shiroiwa Junior High Ninth Grade Class B on what they believe is a school trip. He interacts with his best friend Yoshitoki Kuninobu, who recently confessed a crush on classmate Noriko Nakagawa, and observes the enigmatic Kazuo Kiriyama, leader of the class delinquents, and the scarred transfer student Shogo Kawada. Around ten p.m., the students succumb to knockout gas. Their families are visited by government agents; those who resist are beaten or killed.
The students awaken in a classroom on an island, each wearing a metal collar. Kinpatsu Sakamochi, the government instructor assigned to run the Program, announces that Class B has been selected. When Yoshitoki protests, soldiers shoot him dead; Noriko rushes to his side and is shot in the leg. Shinji Mimura, an athletic and intelligent classmate nicknamed "The Third Man," helps Noriko back to her seat and signals Shuya to stay calm. Sakamochi kills another student with a thrown knife for whispering, then explains the rules: Students leave one by one, each given a daypack containing food, water, a map, and a randomized weapon. The collars track locations and will explode if students enter forbidden zones or if no one dies within 24 hours.
The first classmate to depart, Yoshio Akamatsu, returns with a crossbow and kills another classmate outside the school. Shuya knocks Akamatsu unconscious, grabs Noriko, and flees into the woods. In hiding, Noriko articulates the game's central dilemma: She cannot trust people she does not truly know. This reshapes Shuya's outlook from naïve optimism to cautious realism.
Meanwhile, Kiriyama begins killing systematically, murdering three members of his own gang and a bystander after deciding to play the game based on a coin flip. The narrative reveals that prenatal brain damage left Kiriyama incapable of emotion, making his participation a matter of random choice. Separately, the couple Sakura Ogawa and Kazuhiko Yamamoto leap from a cliff in a double suicide rather than participate. Mitsuko Souma, another classmate, kills Megumi Eto, who had been hiding alone in a village house, by feigning helplessness before striking her with a sickle.
The next morning, classmate Tatsumichi Oki attacks Shuya; during their struggle, Tatsumichi's own hatchet kills him. Kyoichi Motobuchi, the boys' class leader, fires at Shuya, and Kawada intervenes with a shotgun, killing Kyoichi. Kawada joins Shuya and Noriko, explaining that partners provide a survival advantage. Unknown to them, classmate Yuko Sakaki witnesses only the aftermath and becomes convinced Shuya is a murderer. Two friends, Yumiko Kusaka and Yukiko Kitano, use a megaphone to call on everyone to stop fighting, but Kiriyama guns them down.
Kawada reveals he survived the previous year's Program in a different prefecture, making him a two-time participant. He claims to have an escape plan but cannot reveal it until they are the last three alive. He argues that the Program functions to instill distrust among citizens and prevent rebellion. Noriko counters his cynicism, insisting the people are not inherently submissive but simply uninformed.
On another part of the island, Shinji reunites with his best friend Yutaka Seto. Using a laptop and a modified cell phone, Shinji hacks into the government's network and downloads a file that appears to contain the collar codes, but the connection is severed when the government detects the breach. Realizing the collars contain microphones, Shinji devises a backup plan: Build a bomb to destroy the school's control computers and escape by sea. Kiriyama ambushes them during preparations. Yutaka is killed, and the mortally wounded Shinji detonates his bomb but fails to kill Kiriyama, who finishes him off.
Noriko develops a high fever. Shuya insists on reaching a clinic, where Kawada administers antibiotics. Hiroki Sugimura, a classmate searching for classmate Kayoko Kotohiki using a collar-detecting locator device from his daypack, briefly visits but refuses to stay. Kawada gives Hiroki a birdcall, a small device that produces a bird's chirp, as a means of future contact.
Kiriyama ambushes Shuya's group with grenades and machine-gun fire. Shuya draws Kiriyama away so Kawada and Noriko can escape but is shot multiple times and collapses.
Shuya awakens in a lighthouse where Yukie Utsumi and five other classmates have been sheltering. Yukie confesses her feelings for Shuya, and he tells her about Kawada's escape plan. However, Yuko, still convinced Shuya is a killer, poisons the food intended for him. One of the girls, Yuka Nakagawa, accidentally eats the poisoned dish and dies. The remaining girls erupt into paranoid accusations, and within a minute, four of them kill one another in a chain of gunfire. Yuko flees to the lighthouse tower, confesses what she did, and falls to her death despite Shuya's attempt to save her.
Hiroki continues searching and finally locates Kayoko, but she panics and shoots him. Dying, he confesses his love and instructs her to build two signal fires and follow the birdcall to find Shuya's group. Kayoko weeps over his body until Mitsuko arrives and kills her. By the next announcement, only Shuya, Noriko, Kawada, and Kiriyama remain.
Shuya reunites with Kawada and Noriko by following the birdcall. Kiriyama tracks them and a running gun battle ensues. Kawada retrieves an abandoned shotgun and blasts Kiriyama at close range, but Kiriyama rises, protected by a bulletproof vest, and shoots Kawada in the back. Noriko shoots Kiriyama in the face with a revolver, and Kawada delivers a final shotgun blast, killing him.
Kawada then stages his endgame. Having previously hacked the government's systems and learned the collars' internal design, he removes Shuya's and Noriko's collars, sending false death signals. He fires two staged shots for the microphones, making the authorities believe he has won. Shuya and Noriko hide on the island while Kawada boards the winner's ship.
On board, Sakamochi reveals the government deduced Kawada's plan and dispatches a helicopter to gas the island. Shuya and Noriko, who have boarded the ship, attack the soldiers with Kiriyama's submachine gun. Kawada kills Sakamochi by stabbing him in the throat with a pencil. The three reunite on the bridge, but Kawada reveals he is dying from Kiriyama's earlier gunshot wound. He teaches Shuya to steer the ship and asks them not to seek revenge but to live on together. Shuya places the birdcall in Kawada's hand, and Kawada dies.
In the epilogue, Shuya and Noriko receive treatment from a young doctor in Kobe whose own father was mentored by Kawada's father during medical school. They arrange to escape Japan by fishing boat, heading eventually for America. At a train station in Osaka, they watch a news report naming them as wanted; the broadcast includes Kawada's victory video, in which he grins and gives a thumbs-up. Noriko tells Shuya that Kawada once said he was glad to have made such good friends. Shuya pledges to stay with Noriko and to one day dismantle the country's oppressive system. A policeman spots them and fires; Shuya draws his gun, and they flee into the crowd, beginning their life as fugitives.